Chronic granulomatous disease (CGD) is a rare inherited disorder of the NADPH oxidase complex in which phagocytes are defective in generating superoxide anion. NADPH oxidase activation leads to release of sequestered neutrophil granular proteases, which are likely the principal antimicrobial effectors. CGD is characterized by recurrent life-threatening bacterial and fungal infections and by inflammatory complications such as wound dehiscence, obstructive granulomata of the genitourinary tract, and inflammatory bowel disease. Despite routine use of interferon-gamma prophylaxis, fungal infections have remained a persistent problem with an incidence of 0.1 fungal infections per patient year. Invasive pulmonary aspergillosis in CGD manifests with neutrophils and lymphohistiocytic inflammation; hyphal angioinvasion is not observed, indicating that NADPH oxidase-independent pathways appear to be adequate to protect against vascular invasive disease. Chronic prophylaxis with a mould-active agent is standard of care in CGD. “Mulch pneumonitis” is characterized by rapid onset life- pulmonary inflammation following mould exposure, and treated with systemic antifungals and prolonged corticosteroids. Haematopoietic stem cell transplantation is curative in CGD, but transplant-related mortality from GVHD and infectious complications is substantial, particularly in cases of donor/recipient HLA-antigen disparity. Since CGD is a disorder of myeloid stem cells, gene therapy is an attractive option, but maintaining stable population of myeloid gene-corrected cells has been a persistent challenge. The strategy of non-myeloablative conditioning followed by gene therapy facilitates the expansion of gene-corrected cells. Studies of experimental aspergillosis in CGD point to defective tryptophan metabolism as a contributing factor to impaired host defence and increased lung inflammation in CGD.